{"files"=>["https://ndownloader.figshare.com/files/399125", "https://ndownloader.figshare.com/files/399141", "https://ndownloader.figshare.com/files/399171", "https://ndownloader.figshare.com/files/399208"], "description"=>"<div><p>One-third of the world population is infected with <em>Mycobacterium tuberculosis</em> and multi-drug resistant strains are rapidly evolving. The noticeable absence of a whole organism high-throughput screening system for studying the progression of tuberculosis is fast becoming the bottleneck in tuberculosis research. We successfully developed such a system using the zebrafish <em>Mycobacterium marinum</em> infection model, which is a well-characterized model for tuberculosis progression with biomedical significance, mimicking hallmarks of human tuberculosis pathology. Importantly, we demonstrate the suitability of our system to directly study <em>M. tuberculosis</em>, showing for the first time that the human pathogen can propagate in this vertebrate model, resulting in similar early disease symptoms to those observed upon <em>M. marinum</em> infection. Our system is capable of screening for disease progression via robotic yolk injection of early embryos and visual flow screening of late-stage larvae. We also show that this system can reliably recapitulate the standard caudal vein injection method with a throughput level of 2,000 embryos per hour. We additionally demonstrate the possibility of studying signal transduction leading to disease progression using reverse genetics at high-throughput levels. Importantly, we use reference compounds to validate our system in the testing of molecules that prevent tuberculosis progression, making it highly suited for investigating novel anti-tuberculosis compounds <em>in vivo</em>.</p> </div>", "links"=>[], "tags"=>["high-throughput", "tuberculosis", "progression"], "article_id"=>138836, "categories"=>["Microbiology", "Cancer", "Biochemistry", "Developmental Biology", "Immunology"], "users"=>["Ralph Carvalho", "Jan de Sonneville", "Oliver W. Stockhammer", "Nigel D. L. Savage", "Wouter J. Veneman", "Tom H. M. Ottenhoff", "Ron P. Dirks", "Annemarie H. Meijer", "Herman P. Spaink"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0016779.s001", "https://dx.doi.org/10.1371/journal.pone.0016779.s002", "https://dx.doi.org/10.1371/journal.pone.0016779.s003", "https://dx.doi.org/10.1371/journal.pone.0016779.s004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/A_High_Throughput_Screen_for_Tuberculosis_Progression/138836", "title"=>"A High-Throughput Screen for Tuberculosis Progression", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2011-02-16 02:27:16"}